Congestive heart failure is accompanied by both abnormal action of aldosterone on the kidney with failure of "escape" from its action as well as abnormally high rates of secretion and plasma aldosterone concentration resulting in excessive sodium and fluid retention. To determine the biochemical sequence of events after aldosterone administration which results in Na ion reabsorption by the renal tubule, we have developed an isolated perfused kidney preparation which responds to aldosterone administration with increased tubular reabsorption of Na ion accompanied by increased incorporation of H3-leucine into renal microsomal protein and increased incorporation of H3-orotate into RNA. We plan to study the alteration in protein and RNA precursor pools, the characteristics of the aldosterone-stimulated RNA and protein, cofactor and substrate requirements, effect of RNA-synthesis blocking agents, and the quantitative influence of physical factors, such as perfusion pressure alterations and oncotic pressure changes on aldosterone action in this system under carefully controlled conditions. By using a recently developed radioimmunoassay technique for aldosterone concentration determination, coupled with control system block analyses and computer solutions, we will analyze the relative influence of the mechanisms controlling plasma aldosterone concentration under both acute and chronic conditions. We will determine the gain of the system, whether it is under open-loop or closed-loop (negative feedback) control, the characteristics of the feedback signal, the sites of the feedback detectors, and the relative importance by using hemodialysis, of sodium depletion as compared with volume depletion in stimulating aldosterone secretion.